Prolongation of cardiac xenograft function after reduction of natural antibodies using double filtration plasmapheresis.

A double filtration plasmapheresis (DFPP) technique was applied to selectively remove the natural antibodies in discordant xenotransplantation. A swine heart was heterotopically transplanted in a canine neck after two DFPP procedures during which 200 to 500 ml of plasma were replaced with the same amount of Hartman's solution containing 7% human albumin. Mean removal rate of IgC and IgM by DFPP ranged from 74.2 +/- 0.5 to 95.9 +/- 2.8%. The anti-swine lymphocytotoxic reaction of canine serum was decreased after DFPP but still remained in low titers. Mean graft survival time in the group treated by DFPP in which 1000 ml of plasma was totally replaced was prolonged to 107 +/- 47 min, while it was 9 +/- 5 min in the group without any treatment (p less than 0.01). Deposits of canine IgM and C3 on the vascular endothelium of the graft were observed on immunofluorescence, while there were no deposits of IgG. In conclusion, DFPP effectively removed the natural antibodies, resulting in prolongation of xenograft survival time. Immunofluorescence study suggested that natural IgM antibodies played an important role in this xeno-hyperacute rejection.